PURα mediates epithelial-mesenchymal transition to promote esophageal squamous cell carcinoma progression by regulating Snail2

Cancer Lett. 2021 Feb 1:498:98-110. doi: 10.1016/j.canlet.2020.10.030. Epub 2020 Nov 2.

Abstract

Esophageal squamous cell carcinoma (ESCC) is one of the most common lethal cancers in the world. Dysregulation of purine-rich element binding protein alpha (PURα), which contributes to the initiation of PURΑ syndrome, is reportedly involved in the progression of multiple cancers, but its function and underlying mechanisms in ESCC progression remain unclear. Here, we first demonstrated that PURα promoted cell growth, migration and invasion in ESCC both in vitro and in vivo. An immunohistochemistry assay was then performed on 225 ESCC tissues, showing that high PURα expression was positively associated with lymph node metastasis and the AJCC stage, and the ESCC patients with positive PURα expression had worse survival. In addition, RNA sequencing implied that PURα induced epithelial-mesenchymal transition (EMT) in ESCC, which was further confirmed by qPCR, Western blotting and immunofluorescence analyses. Mechanistically, PURα enhanced the transcription of Snail2 by binding to its promoter region. Knockdown of Snail2 reversed PURα-induced EMT and inhibited the migration and invasion of ESCC cells. In conclusion, this study indicated that PURα promotes Snail2 transcriptional activity to induce EMT during ESCC progression.

Keywords: Epithelial-mesenchymal transition; Esophageal squamous cell carcinoma; Migration and invasion; PURα; Snail2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • DNA-Binding Proteins / genetics*
  • Disease Progression
  • Epithelial-Mesenchymal Transition / genetics*
  • Esophageal Neoplasms / genetics*
  • Esophageal Neoplasms / pathology
  • Esophageal Squamous Cell Carcinoma / genetics*
  • Esophageal Squamous Cell Carcinoma / pathology
  • Female
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • Lymphatic Metastasis / genetics
  • Lymphatic Metastasis / pathology
  • Mice
  • Mice, Inbred BALB C
  • Neoplasm Invasiveness / genetics
  • Neoplasm Invasiveness / pathology
  • Promoter Regions, Genetic / genetics
  • Snail Family Transcription Factors / genetics*
  • Transcription Factors / genetics*
  • Transcription, Genetic / genetics

Substances

  • DNA-Binding Proteins
  • PURA protein, human
  • SNAI1 protein, human
  • Snail Family Transcription Factors
  • Transcription Factors